The nature of cellular controls over responses to steroid hormones has been studied through somatic cell hybrids. Processes studied in these hybrids include induction of tyrosine aminotransferase, prolactin, growth hormone and glutamine synthetase and inhibition of nucleic acid uptake, cell growth and cloning efficiency. Steroid-resistant cell variants have been developed. Characterization and purification of glucocorticoid receptors are underway. Receptors for glucocorticoids, androgens, estrogens and progestins, have been studied for their correlation with treatment and disease in human leukemias and breast cancer. Growth control in cell hybrids has been studied and hybrid membrane proteins analyzed. A line of human leukemic cells has been characterized with respect to steroid responsiveness and will be utilized to study the cell genetics of steroid resistance, the mechanism of steroidal lymphocytolysis, and the effects of combined drug therapy in vitro. BIBLIOGRAPHIC REFERENCES: Lyons, Linda B., and Thompson, E. B.: Delayed malignancy and altered growth properties of somatic cell hybrids between rat hepatoma and mouse L-cells. J. Cell. Physiol. 90: 179-192, 1977. Thompson, E. B., Aviv, D., and Lippman, M. E.: Variants of HTC cells with low tyrosine aminotransferase inducibility and apparently normal glucocorticoid receptors. Endocrinology 100: 406-419, 1977.